The long-term objective of this proposal is to establish the number and types of genetic control mechanisms that are utilized in mammals in regulating the activity of specific enzymes and entire pathways. The specific aims of this project are: 1. To study genetic mechanisms involved in the control of gluconeogenesis in mice, specifically those mechanisms involved in regulating glucokinase, serine dehydratase, and phosphoenolpyruvate carboxykinase. 2. To study the relationship between increased rates of gluconeogenesis and the ability to survive fasting in various inbred strains. 3. To determine the rate controlling steps in gluconeogenesis in obese (ob) and diabetes (db) mice which appear to have more efficient methods of utilizing fat and possibly ketone bodies. 4. To study gene dosage with respect to amount of protein produced in certain trisomic stocks, and 5. To study other interesting biochemical mutants that are applicable to our continuing search for new gene systems controlling metabolic pathways.